The goals of this laboratory are to analyze the development and differentiation of B lymphocytes, and to examine some of the regulatory mechanisms of action of immune response (Ir) genes which control the ability of animals to respond to antigen immunization. Present studies indicate that the low-responder status of an animal is not easily modulated by either interaction with high-responder cells or adaptive differentiation of the lymphocytes in appropriate host environments. Our studies also indicate that the Ir genotype of the animal also dictates not only the response to the antigen per se, but also the response to other antigenic determinants which are coupled to the antigen under Ir gene control. A restricted response pattern is therefore obtained to antigens which would normally produce heterogenous, optimal responses. Studies using a mouse strain with a B cell developmental pattern which is abnormal indicate that these animals are not capable of mounting effective antibody responses to antigens under Ir gene control, even though the animal is of high-responder status to that antigen.